Paper BI-TuP7
Proton Transfers Involved in Melanin Biosynthesis: Binding of Cysteine to Dopaquinone Investigated by Density Functional Theory based Calculation

Tuesday, October 31, 2017, 6:30 pm, Room Central Hall

Melanin is a natural pigment present in many types of living organisms. The color of the skin, hair, and eyes is a manifestation of melanin biosynthesis (melanogenesis). Melanogenesis is initiated by oxidation of tyrosine to form reactive dopaquinones. The formed dopaquionone rapidly reacts with cellular cysteine, resulting in the generation of yellow to reddish brown pheomelanin. At lower concentration of cysteine, dopaquionone undergoes intramolecular cyclization, resulting in the generation of brown to black eumelanin. Thus, the reactions of dopaquinone (cyclization and cysteine binding) affect the pheomelanin/eumelanin ratio, determining the body color. The color of eumelanin is further controlled by its monomer ratio. Eumelanin monomers are formed from dopachrome, which is a molecule generated after the stage of dopaquinone.

We have investigated the reactions of dopaquinone and dopachrome [1-4]. In this symposium, we present our recent mechanistic study on reactions of dopaquinone with a focus on the cysteine binding. Using density functional theory based calculation, we computed the energy profiles for the approaching of cysteine to dopaquinone and obtained stable cysteine-bound structures. We found that the cysteine-bound structures can undergo intramolecular proton transfer for further stabilization with fairly small activation energy.

[1] R. Kishida et al., Pigment Cell Melanoma Res. 27 (2014) 734.

[2] R. Kishida et al., Biochim. Biophys. Acta 1850 (2015) 281.

[3] R. Kishida et al., J. Electron. Mater. (2017) doi:10.1007/s11664-017-5299-x.